Cycloisomerization/(2+1) Annulation of Enyne‐Amide With α‐Bromomalonate: A Novel and Selective Access to Oxa/Aza‐Spiro2.4heptane Derivatives

ABSTRACT Oxa‐ and aza‐spiro2.4heptane frameworks are privileged scaffolds in bioactive molecules. Herein, we report a catalyst‐controlled divergent synthesis of these spirocycles from readily accessible enyne‐amides and α‐bromomalonates. Under Au(I) catalysis, cycloisomerization generates a furan‐fused azadiene intermediate, which undergoes base‐promoted (2+1) annulation to afford 5‐oxa‐spiro2.4heptanes with excellent diastereoselectivity (>20:1). In contrast, Pd(II) catalysis triggers an intramolecular hydroamination to form a pyrrole‐fused oxodiene, followed by (2+1) annulation to deliver 5‐aza‐spiro2.4heptanes. This protocol enables selective assembly of diverse spirocyclic products under mild conditions, providing good to excellent yields with high diastereoselectivity.